Cellular growth and differentiation appear to be initiated, promoted, maintained, and regulated by a multiplicity of stimulatory, inhibitory, and synergistic factors and hormones. The alteration and/or breakdown of the cellular homeostasis mechanism seems to be a fundamental cause of growth-related diseases, including neoplasia. Growth modulatory factors are implicated in a wide variety of pathological and physiological processes including signal transduction, cell communication, growth and development, embryogenesis, immune response, hematopoiesis, cell survival and differentiation, inflammation, tissue repair and remodeling, atherosclerosis and cancer.
Epidermal growth factor (EGF), transforming growth factor-.alpha. (TGF.alpha.), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), nerve growth factor (NGF), transforming growth factor-.beta. (TFG.beta.), insulin growth factor I and II (IGF I, IGF II), hematopoietic growth factors such as erythropoietin, colony-stimulating factors (CSF 1 and 2), interleukins (IL-1 to 8), interferons (IFN .alpha., .beta., .gamma.), tumor necrosis factor .alpha. and .beta. (TNF .alpha. and .beta.), leukoregulin, oncostatin M, amphiregulin (AR) and other less defined factors are growth and differentiation modulatory proteins produced by a variety of cell types either under normal physiological conditions or in response to exogenous stimuli. Most of these factors appear to act in autocrine and paracrine fashions. (For reviews see: Goustin et al., 1986, Cancer Res. 46:1015-1029; Rozengurt, 1986, Science 234:161-166; Pardee, 1987, Cancer Res. 47:1488-1491; Sachs, 1986, Sci. Amer. 254:40-47; Marshall, 1987, Cell 50:5-6; Melcher and Anderson, 1987, Cell 30:715-720; Namen et al., 1988, J. Exp. Med. 167:988-1002; Baggiolini et al., 1989, J. Clin. Invest. 84:1045-1049; Clemens and McNurlan, 1985, Biochem, J. 226:345-360; Nathan, 1987, J. Clin. Invest. 79:319-326; Sporn and Roberts, 1986, J. Clin. Invest. 78:329-332; Old, 1987, Nature 326:330-331; Beutler and Cerami, 1987, New Engl. J. Med. 316:379-385; Weinstein, 1987, J. Cell. Biochem. 33:213-224; Zarling et al., 1987, Proc. Natl. Acad. Sci. U.S.A. 83:9739-9744; Shoyab et al., 1988, Proc. Natl. Acad. Sci. U.S.A., 85:6528-6532; Shoyab et al., 1989, Science 243:1074-1076; Sporn and Todaro, 1985, N. Engl. J. Med. 303:878-880; Sporn and Roberts, 1985, Nature 313:745-747).
There is a great deal of interest in isolating, characterizing, and defining the functional mechanisms of growth modulatory factors because of their potential use in the diagnosis, prognosis, and treatment of cancer. Moreover, acquiring knowledge of these factors will aid in the understanding of the basic mechanisms behind normal growth control and the loss thereof in cancer cells.